Mature T lymphocytes arise from intrathymic T-cell precursors, which in turn are derived from a multipotent stem cell in the bone marrow. Unlike bone marrow stem cells, the differentiation potential of the earliest intrathymic precursor cells is strongly biased toward the lymphoid lineage. The major difference in cell surface phenotype between early thymic precursor cells and bone marrow stem cells is that the former population expresses Sca-2. The progeny of the intrathymic precursor population continue to express Sca-2 until the transition from blast cells to small cells, at which stage expression of Sca-2 is down regulated. Mature thymocytes and peripheral T cells do not express detectable levels of Sca-2, whereas peripheral B cells are Sca-2-positive. We report herein the complete sequence of mouse Sca-2 deduced from a thymocyte cDNA clone. Sca-2 is a member of the Ly-6 family, a group of small cysteine-rich cell surface proteins that are anchored in the membrane by a glycosyl-phosphatidylinositol moiety.